Tracking the fate of stem cell implants with fluorine-19 MRI.

BACKGROUND: In this study we used cellular magnetic resonance imaging (MRI) to detect mesenchymal stem cells (MSC) labeled with a Fluorine-19 (19F) agent. 19F-MRI offers unambiguous detection and in vivo quantification of labeled cells. METHODS: We investigated two common stem cell transplant mouse models: an immune competent, syngeneic transplant model and an immune compromised, xenograft transplant model. 19F labelled stem cells were implanted intramuscularly into the hindlimb of healthy mice. The transplant was then monitored for up to 17 days using 19F-MRI, after which the tissue was excised for fluorescence microscopy and immunohistochemisty. RESULTS: Immediately following transplantation, 19F-MRI quantification correlated very well with the expected cell number in both models. The 19F signal decreased over time in both models, with a more rapid decrease in the syngeneic model. By endpoint, only 2/7 syngeneic mice had any detectable 19F signal. In the xenograft model, all mice had detectable signal at endpoint. Fluorescence microscopy and immunohistochemistry were used to show that the 19F signal was related to the presence of bystander labeled macrophages, and not original MSC. CONCLUSIONS: Our results show that 19F-MRI is an excellent tool for verifying the delivery of therapeutic cells early after transplantation. However, in certain circumstances the transfer of cellular label to other bystander cells may confuse interpretation of the long-term fate of the transplanted cells

Invest Radiol

The magnetization-prepared 2 rapid acquisition gradient echo (MP2RAGE) sequence provides quantitative T1 maps in addition to high-contrast morphological images. Advanced acceleration techniques such as compressed sensing (CS) allow its acquisition time to be compatible with clinical applications. To consider its routine use in future neuroimaging protocols, the repeatability of the segmented brain structures was evaluated and compared with the standard morphological sequence (magnetization-prepared rapid gradient echo [MPRAGE]). The repeatability of the T1 measurements was also assessed. Thirteen healthy volunteers were scanned either 3 or 4 times at several days of interval, on a 3 T clinical scanner, with the 2 sequences (CS-MP2RAGE and MPRAGE), set with the same spatial resolution (0.8-mm isotropic) and scan duration (6 minutes 21 seconds). The reconstruction time of the CS-MP2RAGE outputs (including the 2 echo images, the MP2RAGE image, and the T1 map) was 3 minutes 33 seconds, using an open-source in-house algorithm implemented in the Gadgetron framework.Both precision and variability of volume measurements obtained from CAT12 and VolBrain were assessed. The T1 accuracy and repeatability were measured on phantoms and on humans and were compared with literature.Volumes obtained from the CS-MP2RAGE and the MPRAGE images were compared using Student t tests (P < 0.05 was considered significant). The CS-MP2RAGE acquisition provided morphological images of the same quality and higher contrasts than the standard MPRAGE images. Similar intravolunteer variabilities were obtained with the CS-MP2RAGE and the MPRAGE segmentations. In addition, high-resolution T1 maps were obtained from the CS-MP2RAGE. T1 times of white and gray matters and several deep gray nuclei are consistent with the literature and show very low variability (<1%). The CS-MP2RAGE can be used in future protocols to rapidly obtain morphological images and quantitative T1 maps in 3-dimensions while maintaining high repeatability in volumetry and relaxation times.Translational Research and Advanced Imaging LaboratoryDéveloppement de l'IRM ultra-rapide pour la mesure des temps de relaxation : Apllication à la thérapide guidée par IR

Fostering Critical Thinking and Student Participation in Biological Sciences

Instead of giving a lecture that can discourage both students and teachers, let’s try a different way of teaching Biological Sciences by using student participation and critical thinking techniques. Science professors usually perform power point presentations that include hundreds of slides in regards to a specific topic lasting about 2 hours without a break or interruption by student questions. Studies have demonstrated that students, when they participate in class, will memorize information for a longer period of time and develop critical thinking skills. Thus, an interesting approach would be to make students more involved in the course by having interactions between teacher(s) and the student body. To achieve this, analyzing experiments that have been published in international journals would make the course more realistic, and would also allow the students to understand what clinical and academic research has benefited our progress and knowledge base in the field of interest

Les microglies dans une thérapie génique dirigée contre le gliome

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Magn Reson Med

To propose a quantitative 3D double-echo steady-state (DESS) sequence that offers rapid and repeatable T mapping of the human brain using different encoding schemes that account for respiratory B variation. A retrospective self-gating module was firstly implemented into the standard DESS sequence in order to suppress the respiratory artifact via data binning. A compressed-sensing trajectory (CS-DESS) was then optimized to accelerate the acquisition. Finally, a spiral Cartesian encoding (SPICCS-DESS) was incorporated to further disrupt the coherent respiratory artifact. These different versions were compared to a standard DESS sequence (fully DESS) by assessing the T distribution and repeatability in different brain regions of eight volunteers at 3 T. The respiratory artifact correction was determined to be optimal when the data was binned into seven respiratory phases. Compared to the fully DESS, T distribution was improved for the CS-DESS and SPICCS-DESS with interquartile ranges reduced significantly by a factor ranging from 2 to 12 in the caudate, putamen, and thalamus regions. In the gray and white matter areas, average absolute test-retest T differences across all volunteers were respectively 3.5 ± 2% and 3.1 ± 2.1% for the SPICCS-DESS, 4.6 ± 4.6% and 4.9 ± 5.1% for the CS-DESS, and 15% ± 13% and 7.3 ± 5.6% for the fully DESS. The SPICCS-DESS sequence's acquisition time could be reduced by half (<4 min) while maintaining its efficient T mapping. The respiratory-resolved SPICCS-DESS sequence offers rapid, robust, and repeatable 3D T mapping of the human brain, which can be especially effective for longitudinal monitoring of cerebral pathologies.Développement de l'IRM ultra-rapide pour la mesure des temps de relaxation : Apllication à la thérapide guidée par IR

Sci Rep

Iron oxide particles (IOP) are commonly used for Cellular Magnetic Resonance Imaging (MRI) and in combination with several treatments, like Magnetic Fluid Hyperthermia (MFH), due to the rise in temperature they provoke under an Alternating Magnetic Field (AMF). Micrometric IOP have a high sensitivity of detection. Nevertheless, little is known about their internalization processes or their potential heat power. Two micrometric commercial IOP (from Bangs Laboratories and Chemicell) were characterized by Transmission Electron Microscopy (TEM) and their endocytic pathways into glioma cells were analyzed. Their Specific Absorption Rate (SAR) and cytotoxicity were evaluated using a commercial AMF inductor. T2-weighted imaging was used to monitor tumor growth in vivo after MFH treatment in mice. The two micron-sized IOP had similar structures and r relaxivities (100 mM s) but involved different endocytic pathways. Only ScreenMAG particles generated a significant rise in temperature following AMF (SAR = 113 W g Fe). After 1 h of AMF exposure, 60% of ScreenMAG-labeled cells died. Translated to a glioma model, 89% of mice responded to the treatment with smaller tumor volume 42 days post-implantation. Micrometric particles were investigated from their characterization to their intracellular internalization pathways and applied in one in vivo cancer treatment, i.e. MFH.Magnéto-Chimiothérapie : Modélisation de la Délivrance Induite par Champ Magnétique Radiofréquence d'Anticancéreux par des Nano-Vésicules Polymères et Suivi par IRM d'un Modèle de Glioblastom

Early Achilles Enthesis Involvement in a Murine Model of Spondyloarthropathy: Morphological Imaging with Ultrashort Echo-Time Sequences and Ultrasmall Superparamagnetic Iron Oxide (USPIO) Particle Evaluation in Macrophagic Detection

Purpose. To confirm the interest of 3-dimensional ultrashort echo-time (3D-UTE) sequences to assess morphologic aspects in normal and pathological Achilles entheses in a rat model of spondyloarthropathy (SpA) with histological correlations, in comparison with conventional RARE T2 Fat-Sat sequences, and, furthermore, to evaluate the feasibility of a 3D multiecho UTE sequence performed before and after the intravenous injection of ultrasmall superparamagnetic iron oxide (USPIO) particles to assess macrophagic involvement in the Achilles enthesis in the same rat model of SpA. Materials and Methods. Fourteen rats underwent in vivo MRI of the ankle at 4.7 T, including a 3D RARE T2 Fat-Sat sequence and a 3D ultrashort echo-time (UTE) sequence for morphologic assessment at baseline and day 3 after induction of an SpA model, leading to Achilles enthesopathy in the left paw (right paw serving as a control). A 3D multiecho UTE sequence was also performed at day 3 before and then 24 (4 rats) and 48 (2 rats) hours after intravenous injection of USPIO. Visual analysis and signal intensity measurements of all images were performed at different locations of the Achilles enthesis and preinsertional area. Visual analysis and T2∗ measurements were performed before and after USPIO injection, on the 3D multiecho UTE sequence in the same locations. Normal and pathological values were compared by Wilcoxon signed-rank tests. MR findings were compared against histological data. Results. 3D-UTE sequences enabled morphologic identification of the anterior fibrocartilage and posterior collagenic areas of the Achilles enthesis. Visual analysis and signal intensity measurements distinguished SpA-affected entheses from healthy ones at day 3 (P=0.02). After administration of USPIO, no differences in signals were detected. Similarly, both visual analysis and signal T2∗ measurements in the enthesis were unable to distinguish the SpA-affected tendons from healthy ones (P=0.914). Neither the normal anatomy of the enthesis nor its pathological pattern could be distinguished using the standard RARE sequence. Histology confirmed the absence of USPIO in Achilles entheses, despite marked signs of inflammation. Conclusion. Unlike conventional RARE T2 Fat-Sat sequences, 3D-UTE sequences enable morphologic assessment of normal enthesis anatomy and early detection of abnormalities in pathological conditions. However, 3D multiecho UTE sequences combined with USPIO injections with T2∗ measurements were unable to detect macrophagic involvement in these pathological conditions